This proposal has two overall objectives. The first is to determine how arterial smooth muscle cells respond to different growth promoting or growth inhibiting conditions in vivo. To attain this objective, we will need to develop new approaches for measuring cell kinetic parameters. Methods for measuring cell number, cell cycle times, growth fraction, and cell death will be developed for smooth muscle cells stimulated to proliferate in response to arterial endothelial injury (rat carotid drying model). The differences and similarities of smooth muscle cell behavior under a variety of physiological conditions (acute and chronic hypertention, arterial distension, suppression of growth by heparin) will be studied using these methods. The second objective relates to the observation that the sessel wall, even at rest, contains cells in at least two distict growth states: diploid and tetraploid. Our objective is to examine the ontribution of cells in each of the states to the vessel wall proliferative response. The proposed studies will utilize light and electron microscopy, flow cytometry, Feulgen microdensitometry, cell sorting, and cell culture.